HLD-0915 for Prostate Cancer

Recruiting at 4 trial locations

Overseen By Medical Monitor

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Halda Therapeutics OpCo, Inc.

Must be taking: Bisphosphonates, Denosumab

Must not be taking: Corticosteroids, Chemotherapy

Disqualifiers: Bleeding disorder, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

33 Participants Needed

Trial Summary

What is the purpose of this trial?

Assessment of the safety and efficacy of HLD-0915 as monotherapy in patients with metastatic castration resistant prostate cancer (mCRPC) that have progressed on prior systemic therapies, once a recommended dose for expansion (RDE) has been determined in Phase 1 of the trial.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must not have received certain cancer treatments or investigational drugs within 2 weeks before starting the study drug. Some treatments may require a longer period without them before joining the trial.

What safety data exists for HLD-0915 in prostate cancer treatment?

The study on Fas ligand delivery in prostate cancer cells showed that using a specific method reduced overall toxicity, suggesting a safer approach for treatment. ^{1 2 3 4 5}

What makes the drug HLD-0915 unique for treating prostate cancer?

HLD-0915 may be unique due to its potential involvement with the hydroxysteroid dehydrogenase like gene (HSDL1), which is highly expressed in prostate cancer tissues, suggesting a novel target for treatment. This could differentiate it from other treatments that do not target this specific gene expression. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for individuals with metastatic castration-resistant prostate cancer (mCRPC) who have already tried other systemic therapies. Participants should meet specific health criteria set by the researchers.

Inclusion Criteria

Willing and able to adhere to the study visit schedule and other protocol requirements

My prostate cancer diagnosis was confirmed through lab tests.

Life expectancy of at least 3 months

Exclusion Criteria

I have had a major bleeding event recently or have a bleeding disorder.

My tumor shows signs of neuroendocrine or small cell features under the microscope.

I am on a daily steroid dose higher than 10 mg of prednisone.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose-escalation and cohort expansion to determine the maximum tolerated dose and recommended dose for expansion of HLD-0915

21 days per cycle

Multiple visits per cycle for dose-escalation and monitoring

Phase 2 Treatment

Evaluation of anti-tumor activity of HLD-0915 at recommended dose for expansion

21 days per cycle

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• HLD-0915

Trial Overview The study is testing HLD-0915 as a solo treatment to see how safe and effective it is for mCRPC patients after establishing an appropriate dose in the first phase of the trial.

Participant Groups

Group I: HLD-0915 Experimental Treatment 1 Intervention

Oral HLD-0915 administered as a single agent on a 21-day treatment cycle.

Who Is Running the Clinical Trial?

Halda Therapeutics OpCo, Inc.

Lead Sponsor

Trials

1

Recruited

30+

Findings from Research

In a phase I study involving 16 men with hormone refractory prostate cancer, the combination of thalidomide and oral cyclophosphamide was found to be well tolerated, with the most common side effects being mild constipation, peripheral neuropathy, and fatigue.

The treatment showed some efficacy, with 15% of patients experiencing a greater than 50% decrease in prostate-specific antigen (PSA) levels, suggesting potential for further investigation in larger phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalidomide in combination with oral daily cyclophosphamide in patients with pretreated hormone refractory prostate cancer: a phase I clinical trial. Di Lorenzo, G., Autorino, R., De Laurentiis, M., et al.[2020]

In a study of 879 patients with metastatic prostate cancer, BRCA2, ATM, and CDK12 were identified as the most frequently disrupted DNA damage repair genes, found in 15% of cases, indicating potential therapeutic vulnerabilities.

The presence of BRCA2 and CDK12 mutations was linked to poorer clinical outcomes, while the stability of these mutations in both plasma cell-free DNA and archival tissues suggests that ctDNA could be a valuable diagnostic tool for monitoring disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRCA2, ATM, and CDK12 Defects Differentially Shape Prostate Tumor Driver Genomics and Clinical Aggression. Warner, E., Herberts, C., Fu, S., et al.[2022]

In a study of 36 patients with locally advanced prostate cancer and germline DNA damage repair gene defects, the combination of docetaxel and cisplatin chemotherapy showed a significant improvement in biochemical progression-free survival compared to docetaxel alone, with a median bPFS not reached in the cisplatin group versus 7.76 months in the docetaxel group.

The docetaxel plus cisplatin group also demonstrated a higher rate of tumor down-staging (78.57%) compared to the docetaxel group (40.9%), indicating enhanced efficacy, while maintaining a tolerable safety profile with only one case of severe liver insufficiency due to viral hepatitis A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations. Chi, C., Liu, J., Fan, L., et al.[2022]

The study identified PSMA(27) as the most effective peptide for binding to HLA-A2 molecules on dendritic cells, suggesting its potential as a key component in prostate cancer vaccines.

This research is significant as it provides the first evaluation of PSMA peptides based on their binding efficiency to dendritic cells, paving the way for future clinical applications in HLA-A2 positive prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binding of prostate-specific membrane antigen to dendritic cells: a critical step in vaccine preparation. Garetto, S., Sizzano, F., Brusa, D., et al.[2018]

The study developed a prostate-restricted replicative adenovirus (AdIU3) that delivers Fas ligand (FasL) specifically to prostate cancer cells, enhancing its antitumor effects while significantly reducing systemic toxicity compared to traditional methods.

AdIU3 effectively induced apoptosis in prostate cancer cells without harming normal cells, and systemic administration showed no detectable toxicity, unlike the control virus which caused severe harm, demonstrating a safer approach to cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fas ligand delivery by a prostate-restricted replicative adenovirus enhances safety and antitumor efficacy. Li, X., Liu, YH., Zhang, YP., et al.[2018]

In a study of 127 high-risk prostate cancer patients, high expression of PDL1 was found to be common and significantly associated with poorer outcomes, including shorter time to biochemical recurrence (BCR) after treatment.

PDL1 expression serves as an independent prognostic biomarker for high-risk prostate cancer, suggesting that targeting the PD1/PDL1 pathway could be a promising adjuvant therapy following radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Immune Checkpoint Regulator PDL1 is an Independent Prognostic Biomarker for Biochemical Recurrence in Prostate Cancer Patients Following Adjuvant Hormonal Therapy. Li, H., Wang, Z., Zhang, Y., et al.[2020]

The CDCA1 peptide vaccine was well tolerated in a phase I trial with 12 patients suffering from castration-resistant prostate cancer (CRPC), showing no serious adverse events, which highlights its safety profile.

The vaccine induced specific immune responses in patients, with a median overall survival of 11 months, suggesting that it may effectively stimulate the immune system to target CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of cell division associated 1 (CDCA1) peptide vaccination for castration resistant prostate cancer. Obara, W., Sato, F., Takeda, K., et al.[2021]

In a study of 28 patients with high-risk prostate cancer, 50% developed strong immune responses to a vaccine targeting the PSA146-154 peptide, indicating the vaccine's potential to stimulate the immune system against cancer.

Patients who showed enhanced T-cell responses after vaccination had a significantly lower risk of disease progression, and those with specific immune responses tended to have better overall survival rates, averaging 60 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of HLA-A2+ patients with high-risk, hormone-sensitive prostate cancer vaccinated with the prostate specific antigen peptide homologue (PSA146-154). Perambakam, S., Xie, H., Edassery, S., et al.[2021]

In a Phase I clinical trial involving 8 patients with hormone-refractory prostate cancer, a dendritic cell vaccine using a cocktail of prostate cancer-associated peptides was found to be safe, with only minor local skin reactions reported.

One patient achieved a significant reduction in PSA levels (over 50%), while three others had stable or slowed PSA increases, indicating potential efficacy in inducing immune responses against prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial. Fuessel, S., Meye, A., Schmitz, M., et al.[2022]

The novel human gene HSDL1, located on chromosome 16q24.2, encodes a protein related to 17beta-HSD3 and is highly expressed in reproductive tissues like the testis and ovary.

HSDL1 expression is significantly increased in prostate cancer tissues compared to normal prostate tissues, indicating its potential role in the development of prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel human hydroxysteroid dehydrogenase like 1 gene (HSDL1) is highly expressed in reproductive tissues. Huang, Y., Tang, R., Dai, J., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Thalidomide in combination with oral daily cyclophosphamide in patients with pretreated hormone refractory prostate cancer: a phase I clinical trial. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

BRCA2, ATM, and CDK12 Defects Differentially Shape Prostate Tumor Driver Genomics and Clinical Aggression. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Binding of prostate-specific membrane antigen to dendritic cells: a critical step in vaccine preparation. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Fas ligand delivery by a prostate-restricted replicative adenovirus enhances safety and antitumor efficacy. [2018]

6. Australia pubmed.ncbi.nlm.nih.gov

The Immune Checkpoint Regulator PDL1 is an Independent Prognostic Biomarker for Biochemical Recurrence in Prostate Cancer Patients Following Adjuvant Hormonal Therapy. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of cell division associated 1 (CDCA1) peptide vaccination for castration resistant prostate cancer. [2021]

8. Egypt pubmed.ncbi.nlm.nih.gov

Long-term follow-up of HLA-A2+ patients with high-risk, hormone-sensitive prostate cancer vaccinated with the prostate specific antigen peptide homologue (PSA146-154). [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

A novel human hydroxysteroid dehydrogenase like 1 gene (HSDL1) is highly expressed in reproductive tissues. [2019]